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Assessment of the Novel Estrogen Receptor PET Tracer 4-Fluoro-11β-methoxy-16α-[18F]fluoroestradiol (4FMFES) by PET Imaging in a Breast Cancer Murine Model

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Abstract

Purpose

The aim of this study was to compare the in vivo stability, uptake, and positron emission tomography (PET) imaging performance of a novel estrogen receptor PET tracer, 4-fluoro-11β-methoxy-16α-[18F]fluoroestradiol (4FMFES), with 16α-[18F]fluoroestradiol (FES).

Procedures

MC7-L1 and MC4-L2 (ER+) cell lines and their ERα-knockdown variants (ERαKD) were implanted subcutaneously in Balb/c mice. After 21 days, mice were imaged using either FES or 4FMFES. One hour post-injection, static images were acquired for 30 min and the tumor %ID/g uptake values were derived. Biodistribution data were also obtained 1 h following the injection of either FES or 4FMFES. Blood samples were taken at different times and analyzed on thin-layer chromatography to quantify the presence of radiometabolites for each radiotracer. To assess specific targeting to the estrogen receptors, mice bearing only ER+ tumors were treated with the competitive ER inhibitor fulvestrant 48 h prior to imaging with 4FMFES.

Results

Metabolic stability was found to be similar for both tracers in mice. Both FES and 4FMFES differentiated ER+ tumors from ERαKD tumors in biodistribution and PET imaging studies. 4FMFES achieved a significantly higher %ID/g uptake in ER+ tumors and MC4-L2 ERαKD tumors than FES in the PET imaging studies. Also, tumor-to-background ratio was higher in ER+ tumors using 4FMFES compared to FES. Dissection data showed a significantly higher %ID/g in all tested cell lines and ER-rich tissues using 4FMFES versus FES. Fulvestrant-treated mice had either low or undetectable tumor uptake.

Conclusion

In a tumor-bearing mouse model, 4FMFES achieves better specific tumor uptake and better contrast than FES, making it a promising candidate for ER imaging.

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Acknowledgments

We thank Jean-François Beaudoin, Jules Cadorette, and Maxime Paillé for operating and maintaining the LabPET™ scanners. We also thank Mélanie Archambault, Véronique Dumulon-Perrault, and Caroline Mathieu for technical assistance and animal care. This project was supported by the Canadian Institutes of Health Research grant #MOP-86717 and the Canadian Breast Cancer Research Alliance grant #015388.

Conflict of Interest

The authors have no conflict of interest to declare regarding this paper or the results therein.

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Authors and Affiliations

  1. Département de médecine nucléaire et radiobiologie, Sherbrooke Molecular Imaging Center, 3001, 12th Avenue, Sherbrooke, QC, J1H 5N4, Canada

    Michel Paquette, Serge Phoenix, René Ouellet, Réjean Langlois, Johan E. van Lier, Éric E. Turcotte & Roger Lecomte

  2. BC Cancer Agency Research Center, Department of Radiology, University of British Columbia, Vancouver, BC, Canada

    Francois Bénard

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  1. Michel Paquette
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  2. Serge Phoenix
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  3. René Ouellet
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Correspondence to Roger Lecomte.

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Paquette, M., Phoenix, S., Ouellet, R. et al. Assessment of the Novel Estrogen Receptor PET Tracer 4-Fluoro-11β-methoxy-16α-[18F]fluoroestradiol (4FMFES) by PET Imaging in a Breast Cancer Murine Model. Mol Imaging Biol 15, 625–632 (2013). https://doi.org/10.1007/s11307-013-0638-7

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